p-Fluoronitrobenzene → HCID 71483887, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (1R,2R)—N1-((5R)-8-azabicyclo[3.2.1]octan-2-yl)-N2-(5-(4-(trifluoromethoxy)phenyl)oxazol-2-yl)cyclohexane-1,2-diamine (28 mg, 0.062 mmol) and 4-fluoronitrobenzene (9.65 mg, 0.069 mmol) in DMF (0.38 ml) was added K2CO3. The reaction mixture was then heated at 80° C. for 4 hrs. The reaction mixture was partitioned between EtOAc and water. The organic phase was separated, dried over MgSO4, filtered and concentrated. The residue was purified by RP prep-HPLC using method A with two isomers were separating. The fractions with the desired product, which eluted later than the undesired isomer, were concentrated to give (1R,2R)—N1-((6S)-2-(4-nitrophenyl)-2-azabicyclo[2.2.2]octan-6-yl)-N2-(5-(4-(trifluoromethoxy)phenyl)oxazol-2-yl)cyclohexane-1,2-diamine (5.82 mg, 0.0102 mmol, 16.4% yield) as a yellow solid. Anal. Calcd. for C29H32F3N5O4 m/z 571.2, found: 572.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 11.04 (1 H, br. s.), 7.88 (2 H, d, J=9.3 Hz), 7.55 (2 H, d, J=8.2 Hz), 7.30 (2 H, d, J=8.2 Hz), 7.02 (1 H, s), 6.78 (2 H, d, J=9.3 Hz), 6.38 (1 H, br. s.), 4.65 (1 H, d, J=6.0 Hz), 4.36 (1 H, d, J=6.0 Hz), 4.33-4.20 (1 H, m), 3.80-3.73 (1 H, m), 3.40-3.27 (1 H, m), 2.26-1.65 (13 H, m), 1.65-1.30 (3 H, m).

Provenance & Evidence